Synthesis of liponucleotides using bacterial phospholipase D

A series of conjugates of pharmacologically promising modified nucleosides with phospholipid was synthesized. Some liponucleotides were originally produced. Soybean lecithin served as the donor of phosphatidyl residue. Phospholipase D from strain Streptomyces netropsis BIM B-428D was engaged as biocatalyst in transphosphatidylation reaction. The yield of liponucleotide synthesis reaction varied in the range 44–95 mol% depending on the acceptor of phosphatidyl residue. 65 mg (about 68 µmoles) of pure phosphatidylclofarabine was recovered by chromatography on silica gel column, resulting in 68 mol% yield calculated from the amount of modified nucleoside supplied into the reaction mixture.

Keywords:

Phospholipid prodrugs , Streptomyces netropsis , Enzymatic transphosphatidylation , Modified nucleosides , Phosphatidylclofarabine